Chromosomal translocations that produce oncogenic fusion proteins are common in leukemias and soft-tissue tumors but have rarely been observed in solid tumors (carcinomas), which account for 90% of all cancers. In a study of human thyroid follicular carcinomas, Kroll et al. identified a common translocation that fuses the DNA binding region of the PAX8 transcription factor to peroxisome proliferator protein receptor γ1 (PPARγ1), a member of the nuclear hormone receptor superfamily. The fusion protein inhibited transcriptional transactivation by PPARγ1 in a dominant-negative manner. Discovery of this fusion event opens up new possibilities for diagnosis and treatment of thyroid cancer.
Kroll, T.G., Sarraf, P., Pecciarini, L., Chen, C.-J., Mueller, E., Spiegelman, B.M., and Fletcher, J.A. (2000) PAX8-PPARγ1 fusion in oncogene human thyroid carcinoma. Science 289: 1357-1360. [Abstract] [Full Text]